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Background There are over 750,000 cases of severe sepsis and septic shock per year in the US. Short term mortality is estimated to be >20% Many of our current guidelines are based on the 2001 Rivers et al paper – Single-center – Showed that mortality was lower in the population treated according to the 6hr protocol of EGDT (early-goal directed therapy)

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Objective Are all elements of that protocol still applicable a decade later?

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Outcomes Measured Primary end-point was the rate of in-hospital death from ANY cause at 60 days Secondary mortality outcomes – Rate of death from ANY cause at 90 days – Cumulative mortality at 90 days and 1 year Other outcomes – Duration of acute cardiovascular failure (need for vasopressors) – Acute respiratory failure (duration of mech vent – Acute renal failure (duration of HD)

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Incidence of acute renal failure was highest in the Protocol-Based Standard, even though duration of therapy did not differ between groups No significant differences in incidence and duration of cardiovascular failure or respiratory failure or length of stay in hospital

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Results Protocol based care resulted in more use of central venous catheterizations overall. Also increase use of IVF, vasoactive agents and blood transfusion in the initial 6hrs, with little difference between groups thereafter. By 6hrs, more patients in these two groups had reached the target MAP>/=65

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Conclusion “In summary… patients [that] were identified EARLY in the emergency department as having SEPTIC SHOCK and received ANTIBIOTICS and other NONRESUSCITATION aspects of care promptly, we found NO ADVANTAGE, with respect to mortality or morbidity, of protocol-based resuscitation over bedside care… according to the treating physician’s judgment”.

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“Goal-Directed Resuscitation for Patients with Early Septic Shock” The ARISE Investigators and the ANZICS Clinical Trials Group N Engl J Med 2014; 371:1496-1506. October 16, 2014 -Primary end point was 90 day mortality -51 centers in Australia and New Zealand -EGDT v Standard – which did not include SvcO2 monitoring (in first 6hrs) and decisions involving invasive monitoring, IVF rescuscitation, vasoactive support, transfusion and mechanical ventilation were discussed by the treating team